Studies were begun this year on the molecular defect in Hunter Syndrome and the use of human amnion in treatment of the MPS disorders. By classical techniques, iduronate sulfatase was purified several thousand fold from human plasma, representing the first purification to this extent of this enzyme. Plans for studies of the cell biology of this protein are underway. Some 20 children with MPS syndromes were implanted with human amnion epithelium. Initial studies have failed to demonstrate increases in circulating serum lysosomal enzymes, although subjective improvement has been observed in some patients. Studies of the natural history of the disease process in MPS I and II have demonstrated, for the first time, the high incidence of hydrocephalus in these diseases, a process which appears to accelerate CNS deterioration. Further studies on the mechanism of action of thyroid hormone continue. A new method has been developed for the identification of species present in moderate to low abundance in mRNA populations. The method utilizes a contact hybridization procedure previously developed in this laboratory for quantitation of genomic reiteration frequency. Studies on therapeutic utility of 13-cis retinoic acid in the treatment of fibrodysplasia ossificans progessiva (FOP) continue. After a one year pilot utilizing 5 mg/kg/day of this agent, experience with 7 children suggests that the drug is effective in inhibiting formation of new ectopic bone. Treatment studies have been expanded to include a larger population. The utility of this agent in inhibiting new bone formation after surgical intervention is being studied. A new disease process involving the formation of intramembranous bone in the dermal and deeper fascial planes has been delineated, representing a distinctly different condition than FOP.